Differential targeting of Gbetagamma-subunit signaling with small molecules.
Differential targeting of Gbetagamma-subunit signaling with small molecules.
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发表时间：
2006
期刊：
影响因子：
56.9
通讯作者：
Tabetha M. Bonacci;Jennifer L. Mathews;Chujun Yuan;D. Lehmann;S. Malik;Dianqing Wu;Jose L. Font;
中科院分区：
文献类型：
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作者：
Tabetha M. Bonacci;Jennifer L. Mathews;Chujun Yuan;D. Lehmann;S. Malik;Dianqing Wu;Jose L. Font;
G蛋白β γ亚基具有作为许多疾病的治疗性治疗的靶点的潜力。我们进行了虚拟对接的小分子库的一个网站上介导的蛋白质相互作用的γ亚基。我们假设，该表面的差异靶向可以允许选择性调节γ-亚基功能。几种化合物结合到G β γ亚基的亲和力从0.1到60 μ M，并选择性地调节功能性G β γ-蛋白-蛋白质相互作用在体外，在HL-60白细胞趋化肽信号通路，和阿片受体依赖性镇痛在体内。这些数据证明了一种调节G蛋白偶联受体信号传导的方法，这可能是一种重要的治疗策略。
G protein betagamma subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gbetagamma subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gbetagamma subunit functions. Several compounds bound to Gbetagamma subunits with affinities from 0.1 to 60 muM and selectively modulated functional Gbetagamma-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor-dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein-coupled receptor signaling that may represent an important therapeutic strategy.